UNC79 and UNC80, Putative Auxiliary Subunits of the NARROW ABDOMEN Ion Channel, Are Indispensable for Robust Circadian Locomotor Rhythms in Drosophila

Lear, Bridget C.; Darrah, Eric J.; Aldrich, Benjamin T.; Gebre, Senetibeb; Scott, Robert L.; Nash, Howard A.; Allada, Ravi

doi:10.1371/journal.pone.0078147

Cited by 50 publications

(74 citation statements)

References 27 publications

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“…Using empirical JTK_CYCLE (Hutchison et al, 2015), an updated version of JTK_CYCLE (Hughes et al, 2010), to detect rhythmic transcripts at a false discovery rate of 5% (Benjamini-Hochberg corrected p<0.05), we observed robust 24 h rhythms in CG33988, the fly ortholog of the NCA Localization Factor-1 (NLF-1) but not in na itself nor its regulatory subunits unc79 , unc80 (Lear et al, 2013) and NALCN-activators, Src family kinases (Lu et al, 2009), Src42 and Src64b in flies (Fig. 5A).…”

Section: Resultsmentioning

confidence: 99%

A Conserved Bicycle Model for Circadian Clock Control of Membrane Excitability

Flourakis

Kula-Eversole

Hutchison

et al. 2015

Cell

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187

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Summary Circadian clocks regulate membrane excitability in master pacemaker neurons to control daily rhythms of sleep and wake. Here we find that two distinctly timed electrical drives collaborate to impose rhythmicity on Drosophila clock neurons. In the morning, a voltage-independent sodium conductance via the NA/NALCN ion channel depolarizes these neurons. This current is driven by the rhythmic expression of NCA localization factor-1, linking the molecular clock to ion channel function. In the evening, basal potassium currents peak to silence clock neurons. Remarkably, daily antiphase cycles of sodium and potassium currents also drive mouse clock neuron rhythms. Thus, we reveal an evolutionarily ancient strategy for the neural mechanisms that govern daily sleep and wake.

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Section: Resultsmentioning

confidence: 99%

A Conserved Bicycle Model for Circadian Clock Control of Membrane Excitability

Flourakis

Kula-Eversole

Hutchison

et al. 2015

Cell

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187

234

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“…2008; Lear et al. 2013), while Formin‐like protein ( Dmel_CG32138 ) and Dmel_CG17912 are involved in neurogenesis (Sepp et al. 2008; Iyer et al.…”

Section: Resultsmentioning

confidence: 99%

“…There were 11 genes in common between the two studies (Table S5): this overlap was larger than expected of two independent groups but not statistically significant (hypergeometric test: representation factor: 1.3, P = 0.249). Several of these genes have important functions in Drosophila: Phosphogluconate dehydrogenase and cytohesin-1-like are involved in the activation of the mitogen-activated protein kinase (MAPK) (Hahn et al 2013), Juvenile hormone epoxide hydrolase 2 (Jheh2) mediates the catabolism of juvenile hormone (Share and Roe 1988) (but has been co-opted in Apis mellifera to regulate dietary lipid catabolism; Mackert et al 2010), toll like receptor 1 (Toll-1) is an important player in the antimicrobial humoral response and regulation of haemocyte differentiation (Lemaitre et al 1996;Zettervall et al 2004 is involved in apoptosis and response to hypoxia (Azad et al 2009;Chen et al 2012), disc large 1 (dlg1) regulates complex behaviors including phototaxis and circadian activity (Mendoza-Topaz et al 2008), clockwork orange (cwo) and Dmel_CG5237 (unc79) also operate in circadian clock neurons to promote rhythmic behavior (Richier et al 2008;Lear et al 2013), while Formin-like protein (Dmel_CG32138) and Dmel_CG17912 are involved in neurogenesis (Sepp et al 2008;Iyer et al 2013).…”

Section: Transcriptomic Analysis Of Viral Infectionmentioning

confidence: 99%

Dynamic changes in host–virus interactions associated with colony founding and social environment in fire ant queens (Solenopsis invicta)

Manfredini

Shoemaker²,

Grozinger

2015

Ecology and Evolution

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The dynamics of host–parasite interactions can change dramatically over the course of a chronic infection as the internal (physiological) and external (environmental) conditions of the host change. When queens of social insects found a colony, they experience changes in both their physiological state (they develop their ovaries and begin laying eggs) and the social environment (they suddenly stop interacting with the other members of the mother colony), making this an excellent model system for examining how these factors interact with chronic infections. We investigated the dynamics of host–viral interactions in queens of Solenopsis invicta (fire ant) as they transition from mating to colony founding/brood rearing to the emergence of the first workers. We examined these dynamics in naturally infected queens in two different social environments, where queens either founded colonies as individuals or as pairs. We hypothesized that stress associated with colony founding plays an important role in the dynamics of host–parasite interactions. We also hypothesized that different viruses have different modalities of interaction with the host that can be quantified by physiological measures and genomic analysis of gene expression in the host. We found that the two most prevalent viruses, SINV‐1 and SINV‐2, are associated with different fitness costs that are mirrored by different patterns of gene expression in the host. In fact SINV‐2, the virus that imposes the significant reduction of a queen's reproductive output is also associated with larger changes of global gene expression in the host. These results show the complexity of interactions between S. invicta and two viral parasites. Our findings also show that chronic infections by viral parasites in insects are dynamic processes that may pose different challenges in the host, laying the groundwork for interesting ecological and evolutionary considerations.

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“…NCA channels have been shown in recent years to be important for neuronal excitability and a number of rhythmic behaviors [16,[34][35][36][37][38][39][40][41][42]. In humans, mutations affecting the NCA channel NALCN cause neurological diseases [20][21][22][23][24][25][26][27][28][29][30][31][32][33].…”

Section: Discussionmentioning

confidence: 99%

“…In humans, mutations in NALCN or its accessory subunit UNC80 have been associated with a number of neurological symptoms, including cognitive and developmental delay [20][21][22][23][24][25][26][27][28][29][30][31][32][33]. In other organisms, mutations in NALCN/NCA or its accessory subunits lead to defects in rhythmic behaviors [16,[34][35][36][37][38][39][40][41][42]. Specifically in C. elegans, the NCA channels act in premotor interneurons where they regulate persistent motor circuit activity that sustains locomotion [43].…”

Section: Introductionmentioning

confidence: 99%

Dopamine Negatively Modulates the NCA Ion Channels inC. elegans

Topalidou

Cooper

Pereira

et al. 2016

Preprint

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The NALCN/NCA ion channel is a cation channel related to voltage-gated sodium and calcium channels. NALCN has been reported to be a sodium leak channel with a conserved role in establishing neuronal resting membrane potential, but its precise cellular role and regulation are unclear. The Caenorhabditis elegans orthologs of NALCN, NCA-1 and NCA-2, act in premotor interneurons to regulate motor circuit activity that sustains locomotion. Recently we found that NCA-1 and NCA-2 are activated by a signal transduction pathway acting downstream of the heterotrimeric G protein G q and the small GTPase Rho. Through a forward genetic screen, here we identify the GPCR kinase GRK-2 as a new player affecting signaling through the G q -Rho-NCA pathway. Using structure-function analysis, we find that the GPCR phosphorylation and membrane association domains of GRK-2 are required for its function. Genetic epistasis experiments suggest that GRK-2 acts on the D2-like dopamine receptor DOP-3 to inhibit G o signaling and positively modulate NCA-1 and NCA-2 activity. Through cell-specific rescuing experiments, we find that GRK-2 and DOP-3 act in premotor interneurons to modulate NCA channel function. Finally, we demonstrate that dopamine, through DOP-3, negatively regulates NCA activity. Thus, this study identifies a pathway by which dopamine modulates the activity of the NCA channels. Author summaryDopamine is a neurotransmitter that acts in the brain by binding seven transmembrane receptors that are coupled to heterotrimeric GTP-binding proteins (G proteins). Neuronal G proteins often function by modulating ion channels that control membrane excitability. Here we identify a molecular cascade downstream of dopamine in the nematode C. elegans that involves activation of the dopamine receptor DOP-3, activation of the G protein GOA-1, and inactivation of the NCA-1 and NCA-2 ion channels. We also identify a G protein-coupled receptor kinase (GRK-2) that inactivates the dopamine receptor DOP-3, thus leading to inactivation of GOA-1 and activation of the NCA channels. Thus, this PLOS Genetics | https://doi.org/10.1371/journal.pgen

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UNC79 and UNC80, Putative Auxiliary Subunits of the NARROW ABDOMEN Ion Channel, Are Indispensable for Robust Circadian Locomotor Rhythms in Drosophila

Cited by 50 publications

References 27 publications

A Conserved Bicycle Model for Circadian Clock Control of Membrane Excitability

A Conserved Bicycle Model for Circadian Clock Control of Membrane Excitability

Dynamic changes in host–virus interactions associated with colony founding and social environment in fire ant queens (Solenopsis invicta)

Dopamine Negatively Modulates the NCA Ion Channels inC. elegans

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